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Clinical Trial Results:
An open-label, randomized, Phase IV study, to assess the efficacy and safety of tildrakizumab in patients with moderate to severe chronic plaque psoriasis who are non-responders to dimethyl fumarate therapy

Summary
EudraCT number	2019-000817-35
Trial protocol	GB DE NL
Global end of trial date	16 Feb 2022

Results information
Results version number	v1(current)
This version publication date	09 Mar 2023
First version publication date	09 Mar 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

M-14745-41

ISRCTN number

US NCT number

NCT04263610

WHO universal trial number (UTN)

Sponsor organisation name

ALMIRALL, S.A.

Sponsor organisation address

General Mitre, 151, Barcelona, Spain, 08022

Public contact

International Clinical Trial Manager, ALMIRALL, S.A., +34 933128992, valentina.cappello@almirall.com

Scientific contact

International Clinical Trial Manager, ALMIRALL, S.A., +34 933128992, valentina.cappello@almirall.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

16 Feb 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Feb 2022

Was the trial ended prematurely?

Main objective of the trial

The main objective of this trial was to assess the efficacy of tildrakizumab treatment (as assessed by PASI 75) in moderate-to-severe plaque psoriasis patients who are non-responders to dimethyl fumarate (DMF).

Protection of trial subjects

This trial was conducted in accordance with the recommendations guiding physicians in biomedical research involving human patients adopted by the 18th World Medical Assembly of Helsinki (1964), as amended in Fortaleza, Brazil (2013), as well as in compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, and local laws of the countries in which the study centres were located.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Jul 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 183

Country: Number of subjects enrolled

United Kingdom: 6

Worldwide total number of subjects

189

EEA total number of subjects

183

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

179

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Total 189 subjects were randomized in Part 1 out of which 143 completed Part 1 and total 140 subjects were included in Part 2 out of which 129 completed Part 2.

Period 1 title

Part 1

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Dimethyl fumarate standard scheme

Arm description

Participants received DMF standard scheme from baseline to Week 16.

Arm type

Experimental

Investigational medicinal product name

Dimethyl fumarate

Investigational medicinal product code

Other name

Pharmaceutical forms

Gastro-resistant tablet

Routes of administration

Oral use

Dosage and administration details

Participants will receive DMF gastro-resistant tablet orally from baseline to Week 16, at a dose of 30 milligrams (mg) once daily, twice daily, thrice daily in Week 1, Week 2, Week 3 respectively, 120 mg only once in Week 4. Participants will increase DMF dose by 120 mg tablet per week for the subsequent 5 weeks. Participants achieving Psoriasis area and severity Index (PASI) 50-75 (partial responder) or 75 (responder) will continue the DMF treatment until Week 40. The maximum daily dose taken by a participant will be 720 mg.

Simplified DMF treatment scheme

Arm description

Participants achieving a PASI 75 response (responders) and participants failing to achieve a PASI 75 response but having achieved a PASI 50 response (partial responders) at Week 16 continued with DMF treatment until Week 40. Participants failing to achieve a PASI 50 response (non-responders) at Week 16 were treated with Tildrakizumab until Week 40.

Arm type

Experimental

Investigational medicinal product name

Dimethyl fumarate

Investigational medicinal product code

Other name

Pharmaceutical forms

Gastro-resistant tablet

Routes of administration

Oral use

Dosage and administration details

Participants will receive DMF gastro-resistant tablet orally at a dose of 60, 120, 180, 240, 360 mg daily in Week 1, Week 2, Week 3, Week 4, Week 5 respectively, and 480 mg daily from Week 6 to Week 8. If a PASI is greater than or equal to (>=) 30% at Week 8, no dose increase will be done and if PASI is less than (<) 30% at Week 8, participants will receive 600 mg daily in Week 9 and 720 mg from the Week 10 onwards.

Number of subjects in period 1	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Started	143	46
Completed	110	33
Not completed	33	13
Consent withdrawn by subject	7	4
Other	-	1
Adverse event	13	3
Investigator decision	2	-
Withdrawal due to low leukocytes or lymphocytes	1	1
Lost to follow-up	7	1
Non compliance with study drug	1	2
Lack of efficacy	2	1

Period 2 title

Part 2

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

DMF treatment

Arm description

Participants achieving a Psoriasis Area and Severity Index (PASI) 75 response (responders) and participants failing to achieve a PASI 75 response but having achieved a PASI 50 response (partial responders) at Week 16 continued with DMF treatment until Week 40.

Arm type

Experimental

Investigational medicinal product name

Dimethyl fumarate

Investigational medicinal product code

Other name

Pharmaceutical forms

Gastro-resistant tablet

Routes of administration

Oral use

Dosage and administration details

Tildrakizumab treatment

Arm description

Participants who achieve PASI less than (<) 50 (non-responders) at Week 16 received Tildrakizumab subcutaneous injection at a dose of either 100 or 200 mg [(as per the Summary of Product Characteristics (SmPC)] at Weeks 16, 20 and 32 up to Week 40.

Arm type

Experimental

Investigational medicinal product name

Tildrakizumab

Investigational medicinal product code

Other name

Ilumetri®

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Participants who achieve PASI less than (<) 50 (non-responders) at Week 16 will receive Tildrakizumab subcutaneous injection at a dose of either 100 or 200 mg [(as per the Summary of Product Characteristics (SmPC)] at Weeks 16, 20 and 32 up to Week 40.

Number of subjects in period 2 ^[1]	DMF treatment	Tildrakizumab treatment
Started	37	103
Completed	27	102
Not completed	10	1
Consent withdrawn by subject	1	1
Other	1	-
Adverse event	5	-
Withdrawal due to low leukocytes or lymphocytes	1	-
Lost to follow-up	2	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Three subjects who completed Part 1 of the study did not start Part 2

Baseline characteristics

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Reporting group title

Dimethyl fumarate standard scheme

Reporting group description

Participants received DMF standard scheme from baseline to Week 16.

Reporting group title

Simplified DMF treatment scheme

Reporting group description

Reporting group values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme	Total
Number of subjects	143	46	189
Age categorical
Units: Subjects
In utero			0
Preterm newborn infants (gestational age < 37 wks)			0
Newborns (0-27 days)			0
Infants and toddlers (28 days-23 months)			0
Children (2-11 years)			0
Adolescents (12-17 years)			0
Adults (18-64 years)			0
From 65-84 years			0
85 years and over			0
Age continuous
Units: years
arithmetic mean (standard deviation)	43.10 ( 14.01 )	41.57 ( 12.20 )	-
Gender categorical
Units: Subjects
Female	51	21	72
Male	92	25	117

End points

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Reporting group title

Dimethyl fumarate standard scheme

Reporting group description

Participants received DMF standard scheme from baseline to Week 16.

Reporting group title

Simplified DMF treatment scheme

Reporting group description

Reporting group title

DMF treatment

Reporting group description

Reporting group title

Tildrakizumab treatment

Reporting group description

Primary: Part 2: Percentage of subjects who were non-responders to DMF at Week 16 that were treated with tildrakizumab and achieved a PASI 75 at Week 40

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End point title

Part 2: Percentage of subjects who were non-responders to DMF at Week 16 that were treated with tildrakizumab and achieved a PASI 75 at Week 40 ^[1]

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). PASI 75 response, is defined as having an improvement (reduction) of greater than or equal to (>=) 75% in PASI score compared to the baseline score. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication.

End point type

Primary

End point timeframe

Up to Week 40

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analysed for this endpoint.

End point values	Tildrakizumab treatment
Number of subjects analysed	101
Units: percentage of subjects
number (not applicable)	77.2

No statistical analyses for this end point

Secondary: Part 1: Percentage of subjects achieving PASI 50, PASI 75 and PASI 90 responses at Week 8 and Week 16 Visits

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End point title

Part 1: Percentage of subjects achieving PASI 50, PASI 75 and PASI 90 responses at Week 8 and Week 16 Visits

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). PASI 50, 75, 90 response, is defined as having an improvement (reduction) of greater than or equal to (>=) 50%, 75%, 90% and 100% respectively in PASI score compared to the baseline score. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: percentage of subjects
number (not applicable)
PASI 50 at Week 8	20.3	21.6
PASI 75 at Week 8	4.2	2.7
PASI 90 at Week 8	0.0	2.7
PASI 50 at Week 16	28.8	27.3
PASI 75 at Week 16	12.6	15.2
PASI 90 at Week 16	4.5	6.1

No statistical analyses for this end point

Secondary: Part 1: Percentage of subjects achieving absolute PASI scores of ≤5, ≤3 and ≤1 at Week 8 and Week 16 Visits

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End point title

Part 1: Percentage of subjects achieving absolute PASI scores of ≤5, ≤3 and ≤1 at Week 8 and Week 16 Visits

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). Percentage of participants who achieved an absolute PASI score <= 5, 3 and 1 at Week 8 and Week 16 is reported. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: percentage of subjects
number (not applicable)
PASI ≤5 at Week 8	6.8	10.8
PASI ≤3 at Week 8	2.5	2.7
PASI ≤1 at Week 8	0.0	0.0
PASI ≤5 at Week 16	25.2	18.2
PASI ≤3 at Week 16	11.7	15.2
PASI ≤1 at Week 16	4.5	6.1

No statistical analyses for this end point

Secondary: Part 1: Absolute PASI score at Week 8 and Week 16 Visits

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End point title

Part 1: Absolute PASI score at Week 8 and Week 16 Visits

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, n is defined as number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 118, 37)	12.97 ( 8.31 )	11.63 ( 5.77 )
Week 16 (n= 111, 33)	11.42 ( 8.22 )	11.41 ( 7.03 )

No statistical analyses for this end point

Secondary: Part 1: Change from baseline in the absolute PASI score at Week 8 and Week 16 Visits

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End point title

Part 1: Change from baseline in the absolute PASI score at Week 8 and Week 16 Visits

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline is calculated by subtracting post-dose value baseline value. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline, Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 118, 37)	-3.87 ( 5.79 )	-5.52 ( 4.98 )
Week 16 (n= 111, 33)	-5.42 ( 5.76 )	-5.82 ( 5.63 )

No statistical analyses for this end point

Secondary: Part 1: Absolute Body Surface Area (BSA) Score at Week 8 and Week 16 Visits

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End point title

Part 1: Absolute Body Surface Area (BSA) Score at Week 8 and Week 16 Visits

End point description

BSA is a numerical score used to measure the total area of the body affected by psoriasis. The palm method will be applied: the participant's palm, including the five digits is used as a reference (representing approximately 1% of the total body surface area) and is used to repeatedly cover the lesions on the body. The investigator totals the number of palms required and then estimates the percentage (%) in each of the four body regions: head (including scalp) and neck (10%); upper extremities (20%); trunk (30%); and lower extremities (40%). The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 118, 37)	18.09 ( 15.29 )	17.36 ( 12.46 )
Week 16 (n= 111, 33)	16.58 ( 16.76 )	16.39 ( 13.16 )

No statistical analyses for this end point

Secondary: Part 1: Change from Baseline in Absolute Body Surface Area (BSA) Score at Week 8 and Week 16 Visits

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End point title

Part 1: Change from Baseline in Absolute Body Surface Area (BSA) Score at Week 8 and Week 16 Visits

End point description

BSA is a numerical score used to measure the total area of the body affected by psoriasis. The palm method will be applied: the participant's palm, including the five digits is used as a reference (representing approximately 1% of the total body surface area) and is used to repeatedly cover the lesions on the body. The investigator totals the number of palms required and then estimates the percentage (%) in each of the four body regions: head (including scalp) and neck (10%); upper extremities (20%); trunk (30%); and lower extremities (40%). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline is calculated by subtracting post-dose value baseline value. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline, Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 118, 37)	-2.68 ( 9.83 )	-3.44 ( 6.05 )
Week 16 (n= 111, 33)	-4.43 ( 9.22 )	-5.45 ( 8.05 )

No statistical analyses for this end point

Secondary: Part 1: Percentage of subjects achieving PGA scores of 0 or 1 at Week 8 and Week 16 Visits

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End point title

Part 1: Percentage of subjects achieving PGA scores of 0 or 1 at Week 8 and Week 16 Visits

End point description

The PGA score is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions will be graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales will be divided by 3 to obtain final PGA score. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: percentage of subjects
number (not applicable)
Week 8 (n= 118, 37)	5.9	8.1
Week 16 (n= 111, 33)	14.4	24.2

No statistical analyses for this end point

Secondary: Part 1: Percentage of subjects achieving Scalp Physician Global Assessment (scPGA) and Palmoplantar Physician's Global Assessment (PPPGA) Scores of 0 or 1 at Week 8 and Week 16 Visits

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End point title

Part 1: Percentage of subjects achieving Scalp Physician Global Assessment (scPGA) and Palmoplantar Physician's Global Assessment (PPPGA) Scores of 0 or 1 at Week 8 and Week 16 Visits

End point description

The scPGA score is used to assess the average severity of scalp psoriasis lesions. The scPGA is also 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe scalp psoriasis lesions. Only in participants with scalp involvement, the scPGA assessment was performed. The PPPGA score is used to assess the average severity of severity of psoriasis lesions on hands and/or feet. The PPPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe psoriasis lesions on hands and/or feet. Only in participants with palmar or plantar involvement the PPPGA assessment was performed. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: percentage of subjects
number (not applicable)
PPPGA (0,1) at Week 8 (n= 109, 34)	81.7	76.5
ScPGA (0,1) at Week 8 (n= 117, 36)	28.2	36.1
PPPGA (0,1) at Week 16 (n= 101, 30)	84.2	76.7
ScPGA (0,1) at Week 16 (n= 108, 32)	38.0	43.8

No statistical analyses for this end point

Secondary: Part 1: Absolute PGA scores at Week 8 and Week 16 Visits

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End point title

Part 1: Absolute PGA scores at Week 8 and Week 16 Visits

End point description

The PGA score is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions is graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales is divided by 3 to obtain final PGA score. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 118, 37)	2.72 ( 0.82 )	2.54 ( 0.84 )
Week 16 (n= 111, 33)	2.44 ( 1.02 )	2.45 ( 1.12 )

No statistical analyses for this end point

Secondary: Part 1: Absolute ScPGA and PPPGA scores at Week 8 and Week 16 Visits

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End point title

Part 1: Absolute ScPGA and PPPGA scores at Week 8 and Week 16 Visits

End point description

The scPGA score is used to assess the average severity of scalp psoriasis lesions. The scPGA is also 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe scalp psoriasis lesions. Only in participants with scalp involvement, the scPGA assessment was performed. The PPPGA score is used to assess the average severity of psoriasis lesions on hands and/or feet. The PPPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe psoriasis lesions on hands and/or feet. Only in participants with palmar or plantar involvement the PPPGA assessment was performed. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
ScPGA at Week 8 (n= 117, 36)	2.03 ( 1.20 )	1.86 ( 1.38 )
PPPGA at Week 8 (n= 109, 34)	0.54 ( 1.03 )	0.74 ( 1.40 )
ScPGA at Week 16 (n= 117, 36)	1.81 ( 1.26 )	1.41 ( 1.34 )
PPPGA at Week 16 (n= 101, 30)	0.42 ( 0.89 )	0.70 ( 1.26 )

No statistical analyses for this end point

Secondary: Part 1: Change from baseline in the absolute PGA scores at Week 8 and Week 16 Visits

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End point title

Part 1: Change from baseline in the absolute PGA scores at Week 8 and Week 16 Visits

End point description

The PGA score is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions was graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales was divided by 3 to obtain final PGA score. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline was calculated by subtracting post-dose value baseline value. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline, Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 118, 37)	-0.49 ( 0.80 )	-0.65 ( 0.59 )
Week 16 (n= 111, 33)	-0.77 ( 1.00 )	-0.76 ( 0.87 )

No statistical analyses for this end point

Secondary: Part 1: Change from baseline in the absolute ScPGA and PPPGA scores at Week 8 and Week 16 Visits

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End point title

Part 1: Change from baseline in the absolute ScPGA and PPPGA scores at Week 8 and Week 16 Visits

End point description

The scPGA score is used to assess the average severity of scalp psoriasis lesions. The scPGA is also 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe scalp psoriasis lesions. Only in participants with scalp involvement, the scPGA assessment was performed. The PPPGA score is used to assess the average severity of psoriasis lesions on hands and/or feet. The PPPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe psoriasis lesions on hands and/or feet. Only in participants with palmar or plantar involvement the PPPGA assessment was performed. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline was calculated by subtracting post-dose value baseline value. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value.

End point type

Secondary

End point timeframe

Baseline, Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
PPPGA at Week 8 (n= 102, 33)	-0.09 ( 0.86 )	-0.03 ( 0.47 )
ScPGA at Week 8 (n= 115, 36)	-0.52 ( 0.98 )	-0.50 ( 0.78 )
PPPGA at Week 16 (n= 96, 29)	-0.17 ( 0.90 )	-0.03 ( 0.82 )
ScPGA at Week 16 (n= 107, 32)	-0.74 ( 1.23 )	-1.09 ( 1.38 )

No statistical analyses for this end point

Secondary: Part 1: Percentage of subjects achieving Dermatology Quality of Life Index (DLQI) scores of 0 or 1 at Week 8 and Week 16 Visits

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End point title

Part 1: Percentage of subjects achieving Dermatology Quality of Life Index (DLQI) scores of 0 or 1 at Week 8 and Week 16 Visits

End point description

DLQI is a questionnaire which is to evaluate the impact on participant's quality of life due to psoriasis. It is composed of ten items related to symptoms, feelings, daily activities, leisure, working or studying activities, personal relationships and opinions about dermatological treatment. Each item is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: percentage of subjects
number (not applicable)
Week 8	8.7	5.6
Week 16	16.5	15.2

No statistical analyses for this end point

Secondary: Part 1: Absolute DLQI score at Week 8 and Week 16 Visits

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End point title

Part 1: Absolute DLQI score at Week 8 and Week 16 Visits

End point description

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 115, 36)	10.58 ( 7.23 )	8.44 ( 5.47 )
Week 16 (n= 109, 33)	9.33 ( 7.65 )	5.73 ( 4.35 )

No statistical analyses for this end point

Secondary: Part 1: Change from baseline in the absolute DLQI score at Week 8 and Week 16 Visits

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End point title

Part 1: Change from baseline in the absolute DLQI score at Week 8 and Week 16 Visits

End point description

DLQI is a questionnaire which is to evaluate the impact on participant's quality of life due to psoriasis. It is composed of ten items related to symptoms, feelings, daily activities, leisure, working or studying activities, personal relationships and opinions about dermatological treatment. Each item is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline is calculated by subtracting post-dose value baseline value. ITT population included and "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline, Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 114, 35)	-2.07 ( 5.63 )	-3.49 ( 4.92 )
Week 16 (n= 109, 32)	-3.32 ( 6.81 )	-6.50 ( 6.87 )

No statistical analyses for this end point

Secondary: Part 1: Absolute Skindex-16 score at Week 8 and Week 16 Visits

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End point title

Part 1: Absolute Skindex-16 score at Week 8 and Week 16 Visits

End point description

Skindex is the dermatological instruments to measure dermatology-specific Health-Related Quality of Life (HRQoL). The 16-item Skindex questionnaire is divided into three domains: questions related to the participant's symptoms (1-4), emotions (5-11), and functioning (12-16). Each question asks the participant to quantify how much a specific aspect of their skin condition bothered them in the week prior to administration of the Skindex-16. The questions are answered on a scale from 0 (never bothered) to 6 (always bothered) with a total possible score ranging from 0 (best HRQoL) to 96 (worst HRQoL). Each item is then transformed to a linear scale from 0 to 100. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 116, 36)	51.93 ( 27.43 )	45.01 ( 23.20 )
Week 16 (n= 109, 33)	45.26 ( 29.21 )	37.19 ( 23.15 )

No statistical analyses for this end point

Secondary: Part 1: Change from baseline in the absolute Skindex-16 score at Week 8 and Week 16 Visits

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End point title

Part 1: Change from baseline in the absolute Skindex-16 score at Week 8 and Week 16 Visits

End point description

Skindex is the best dermatological instruments to measure dermatology-specific Health-Related Quality of Life (HRQoL). The 16-item Skindex questionnaire is divided into three domains: questions related to the participant's symptoms (1-4), emotions (5-11), and functioning (12-16). Each question asks the participant to quantify how much a specific aspect of their skin condition bothered them in the week prior to administration of the Skindex-16. The questions are answered on a scale from 0 (never bothered) to 6 (always bothered) with a total possible score ranging from 0 (best HRQoL) to 96 (worst HRQoL). Each item is then transformed to a linear scale from 0 to 100. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline is calculated by subtracting post-dose value baseline value. ITT population included and "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline, Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 116, 36)	-8.69 ( 20.42 )	-14.80 ( 18.73 )
Week 16 (n= 109, 33)	-14.77 ( 25.13 )	-23.54 ( 28.22 )

No statistical analyses for this end point

Secondary: Part 1: Absolute pruritus-VAS score at Week 8 and Week 16 Visits

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End point title

Part 1: Absolute pruritus-VAS score at Week 8 and Week 16 Visits

End point description

The pruritus-VAS is used to assess the pruritus by ticking the scale, which describes pruritus the best. The pruritus-VAS is a single-item continuous scale comprised of a 10 centimeter (cm) [(100 millimeter (mm)] horizontal/vertical line anchored by two verbal descriptors, one for each symptom extreme. For pruritus intensity, the scale is anchored by "no pruritus" (score of 0) and "worst imaginable pruritus" (score of 100 mm). The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 117, 36)	5.06 ( 2.65 )	4.69 ( 2.51 )
Week 16 (n= 110, 33)	4.63 ( 2.97 )	3.91 ( 2.38 )

No statistical analyses for this end point

Secondary: Part 1: Change from baseline in the absolute pruritus-VAS score at Week 8 and Week 16 Visits

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End point title

Part 1: Change from baseline in the absolute pruritus-VAS score at Week 8 and Week 16 Visits

End point description

The pruritus-VAS is used to assess the pruritus by ticking the scale, which describes pruritus the best. The pruritus-VAS is a single-item continuous scale comprised of a 10 centimeter (cm) [(100 millimeter (mm)] horizontal/vertical line anchored by two verbal descriptors, one for each symptom extreme. For pruritus intensity, the scale is anchored by "no pruritus" (score of 0) and "worst imaginable pruritus" (score of 100 mm). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline is calculated by subtracting post-dose value baseline value. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline, Week 8 and 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Week 8 (n= 117, 36)	-0.89 ( 2.81 )	-0.31 ( 3.23 )
Week 16 (n= 110, 33)	-1.27 ( 3.22 )	-1.33 ( 3.57 )

No statistical analyses for this end point

Secondary: Part 1: Absolute Medical Outcomes Study Score (MOSS) at Week 16 Visit

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End point title

Part 1: Absolute Medical Outcomes Study Score (MOSS) at Week 16 Visit

End point description

The MOSS questionnaire consists of 12 items leading to 6 subscales or domains: sleep disturbance, sleep adequacy, daytime sleepiness, 'supposed or known' snoring, being awakened by shortness of breath or by a headache, and quantity of sleep. Subscales are standardized to yield scores from 0 to 100, with the exception of sleep quantity. Higher scores on the MOSS reflects more of the attribute indicated by the subscale name. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value.

End point type

Secondary

End point timeframe

Week 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	110	33
Units: units on a scale
arithmetic mean (standard deviation)
Disturbance	38.30 ( 21.45 )	33.71 ( 15.78 )
Quantity	6.73 ( 1.27 )	6.82 ( 0.98 )
Adequacy	56.59 ( 24.75 )	57.58 ( 21.86 )
Shortness of breath/headache	22.05 ( 24.36 )	18.18 ( 19.03 )
Snoring	43.64 ( 35.59 )	38.64 ( 27.31 )
Somnolence	35.08 ( 22.30 )	32.32 ( 16.50 )

No statistical analyses for this end point

Secondary: Part 1: Change from baseline in the absolute MOSS score at Week 16 Visits

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End point title

Part 1: Change from baseline in the absolute MOSS score at Week 16 Visits

End point description

The MOSS questionnaire consists of 12 items leading to 6 subscales or domains: sleep disturbance, sleep adequacy, daytime sleepiness, 'supposed or known' snoring, being awakened by shortness of breath or by a headache, and quantity of sleep. Subscales are standardised to yield scores from 0 to 100, with the exception of sleep quantity. Higher scores on the MOSS reflects more of the attribute indicated by the subscale name. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline is calculated by subtracting post-dose value baseline value. The intention-to-treat (ITT) population for Part 1 was defined as all included patients who took at least one dose of the study medication in Part 1 of the study and had at least one efficacy baseline value.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Dimethyl fumarate standard scheme	Simplified DMF treatment scheme
Number of subjects analysed	143	46
Units: units on a scale
arithmetic mean (standard deviation)
Disturbance	-4.09 ( 19.65 )	-1.52 ( 15.15 )
Quantity	0.08 ( 1.20 )	0.00 ( 0.79 )
Adequacy	1.82 ( 19.95 )	-1.52 ( 25.15 )
Shortness of breath/headache	2.73 ( 19.56 )	-4.55 ( 26.85 )
Snoring	-3.18 ( 26.69 )	5.30 ( 21.43 )
Somnolence	2.42 ( 18.70 )	3.79 ( 15.60 )

No statistical analyses for this end point

Secondary: Part 2: Percentage of subjects achieving PASI 50, PASI 75 and PASI 90 responses

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End point title

Part 2: Percentage of subjects achieving PASI 50, PASI 75 and PASI 90 responses

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). PASI 50, 75, 90 response, is defined as having an improvement (reduction) of greater than or equal to (>=) 50%, 75%, and 90% respectively in PASI score compared to the baseline score. Here, 99999 indicates that there were no observes cases at specified timepoint for the group. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 20/24; Week 32/36; Week 40; End of Study

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percentage of subjects
number (not applicable)
PASI 50 at Week 20/24 (n=37,100)	97.3	58.0
PASI 75 at Week 20/24 (n=37,100)	75.7	21.0
PASI 90 at Week 20/24 (n=37,100)	29.7	8.0
PASI 50 at Week 32/36 (n=30,103)	96.7	89.3
PASI 75 at Week 32/36 (n=30,103)	73.3	70.9
PASI 90 at Week 32/36 (n=30,103)	33.3	48.5
PASI 50 at Week 40 (n=30,101)	100.0	95.0
PASI 75 at Week 40 (n=30,101)	80.0	77.2
PASI 90 at Week 40 (n=30,101)	33.3	54.5
PASI 50 at EOS (n=5,0)	100.0	99999
PASI 75 at EOS (n=5,0)	80.0	99999
PASI 90 at EOS (n=5,0)	20.0	99999

No statistical analyses for this end point

Secondary: Part 2: Percentage of subjects achieving absolute PASI scores of ≤5, ≤3 and ≤1

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End point title

Part 2: Percentage of subjects achieving absolute PASI scores of ≤5, ≤3 and ≤1

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication.Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 20/24; Week 32/36; Week 40; End of Study

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percentage of subjects
number (not applicable)
PASI ≤ 5 at Week 20/24 (n=37,100)	86.5	30.0
PASI ≤ 3 at Week 20/24 (n=37,100)	64.9	14.0
PASI ≤ 1 at Week 20/24 (n=37,100)	27.0	5.0
PASI ≤ 5 at Week 32/36 (n=30,103)	83.3	75.7
PASI ≤ 3 at Week 32/36 (n=30,103)	66.7	66.0
PASI ≤ 1 at Week 32/36 (n=30,103)	26.7	36.9
PASI ≤ 5 at Week 40 (n=30,101)	86.7	84.2
PASI ≤ 3 at Week 40 (n=30,101)	73.3	68.3
PASI ≤ 1 at Week 40 (n=30,101)	23.3	45.5
PASI ≤ 5 at EOS (n=5,0)	100.0	99999
PASI ≤ 3 at EOS (n=5,0)	60.0	99999
PASI ≤ 1 at EOS (n=5,0)	0.0	99999

No statistical analyses for this end point

Secondary: Part 2: Absolute PASI score at each visit

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End point title

Part 2: Absolute PASI score at each visit

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: units on a scale
arithmetic mean (standard deviation)
Week 20/24 (n= 37, 100)	2.81 ( 2.88 )	8.67 ( 7.26 )
Week 32/36 (n= 30, 103)	2.41 ( 1.95 )	3.56 ( 5.11 )
Week 40 (n= 30, 101)	2.41 ( 1.94 )	2.77 ( 4.42 )

No statistical analyses for this end point

Secondary: Part 2: Change from baseline in the absolute PASI score at each visit

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End point title

Part 2: Change from baseline in the absolute PASI score at each visit

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline is calculated by subtracting post-dose value baseline value. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline; Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: units on a scale
arithmetic mean (standard deviation)
Week 20/24 (n= 37, 100)	-12.06 ( 5.41 )	-9.38 ( 6.55 )
Week 32/36 (n= 30, 103)	-12.49 ( 5.36 )	-14.31 ( 6.96 )
Week 40 (n= 30, 101)	-12.49 ( 4.96 )	-14.91 ( 6.77 )

No statistical analyses for this end point

Secondary: Part 2: Percent change from baseline in the absolute PASI score at each visit

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End point title

Part 2: Percent change from baseline in the absolute PASI score at each visit

End point description

PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Percent Change from Baseline=Change from baseline/baseline value*100. If baseline value was 0, percent change from baseline was not computed. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline; Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percent change
arithmetic mean (standard deviation)
Week 20/24 (n= 37, 100)	-80.12 ( 18.61 )	-52.20 ( 26.15 )
Week 32/36 (n= 30, 103)	-82.74 ( 14.00 )	-81.41 ( 19.15 )
Week 40 (n= 30, 101)	-83.38 ( 12.53 )	-85.66 ( 16.08 )

No statistical analyses for this end point

Secondary: Part 2: Absolute Body Surface Area (BSA) Score at each visit

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End point title

Part 2: Absolute Body Surface Area (BSA) Score at each visit

End point description

BSA is a numerical score used to measure the total area of the body affected by psoriasis. The palm method will be applied: the participant's palm, including the five digits is used as a reference (representing approximately 1% of the total body surface area) and is used to repeatedly cover the lesions on the body. The investigator totals the number of palms required and then estimates the percentage (%) in each of the four body regions: head (including scalp) and neck (10%); upper extremities (20%); trunk (30%); and lower extremities (40%). The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: units on a scale
arithmetic mean (standard deviation)
Week 20/24 (n= 37, 100)	3.44 ( 3.37 )	14.88 ( 12.66 )
Week 32/36 (n= 30, 103)	2.49 ( 2.99 )	5.92 ( 7.67 )
Week 40 (n= 30, 101)	2.20 ( 2.35 )	3.87 ( 6.12 )

No statistical analyses for this end point

Secondary: Part 2: Change from baseline in the absolute BSA score at each visit

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End point title

Part 2: Change from baseline in the absolute BSA score at each visit

End point description

BSA is a numerical score used to measure the total area of the body affected by psoriasis. The palm method will be applied: the participant's palm, including the five digits is used as a reference (representing approximately 1% of the total body surface area) and is used to repeatedly cover the lesions on the body. The investigator totals the number of palms required and then estimates the percentage (%) in each of the four body regions: head (including scalp) and neck (10%); upper extremities (20%); trunk (30%); and lower extremities (40%).The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline; Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	100
Units: units on a scale
arithmetic mean (standard deviation)
Week 20/24 (n=37,100)	-14.90 ( 12.43 )	-7.82 ( 12.10 )
Week 32/36 (n=30,103)	-15.67 ( 11.48 )	-16.45 ( 16.82 )
Week 40 (n=30,101)	-15.96 ( 11.80 )	-18.23 ( 17.50 )

No statistical analyses for this end point

Secondary: Part 2: Percentage of subjects achieving PGA scores of 0 or 1 at each visit

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End point title

Part 2: Percentage of subjects achieving PGA scores of 0 or 1 at each visit

End point description

The PGA score is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions is graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales is divided by 3 to obtain final PGA score.The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline; Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percentage of subjects
number (not applicable)
Week 20/24 (n=37,100)	56.8	34.0
Week 32/36 (n=30,103)	50.0	70.9
Week 40 (n=30,100)	50.0	78.0

No statistical analyses for this end point

Secondary: Part 2: Percentage of subjects achieving ScPGA and PPPGA scores of 0 or 1 at each visit

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End point title

Part 2: Percentage of subjects achieving ScPGA and PPPGA scores of 0 or 1 at each visit

End point description

The scPGA score is used to assess the average severity of scalp psoriasis lesions. The scPGA is also 5- point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe scalp psoriasis lesions. Only in participants with scalp involvement, scPGA assessment was performed. The PPPGA score is used to assess the average severity of psoriasis lesions on hands and/or feet. The PPPGA is 5- point scale ranging from 0 (clear) to 4 (severe), where higher score indicates severe psoriasis lesions on hands and/or feet. Only in participants with palmar or plantar involvement the PPPGA assessment was performed. Baseline value is defined as values collected at Week 1 of Part 1 of study. Change from baseline is calculated by subtracting post-dose value baseline value. The ITT population for Part 2 was defined as all patients entering Part 2 of study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline; Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percentage of subjects
number (not applicable)
PPPGA (0,1) at Week 20/24 (n=31,97)	93.5	84.5
ScPGA (0,1) at Week 20/24 (n=35,99)	74.3	47.5
PPPGA (0,1) at Week 32/36 (n=25,101)	92.0	94.1
ScPGA (0,1) at Week 32/36 (n=27,102)	70.4	72.5
PPPGA (0,1) at Week 40 (n=27,99)	92.6	91.9
ScPGA (0,1) at Week 40 (n=30,100)	63.3	79.0

No statistical analyses for this end point

Secondary: Part 2: Absolute PGA scores at each visit

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End point title

Part 2: Absolute PGA scores at each visit

End point description

The PGA score is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions is graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales is divided by 3 to obtain final PGA score. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: units on a scale
arithmetic mean (standard deviation)
Week 20/24 (n= 37, 100)	1.35 ( 0.86 )	1.91 ( 0.88 )
Week 32/36 (n= 30, 103)	1.40 ( 1.00 )	1.22 ( 0.91 )
Week 40 (n= 30, 100)	1.57 ( 1.04 )	0.93 ( 0.90 )

No statistical analyses for this end point

Secondary: Part 2: Percent change from baseline in the absolute PGA scores at each visit

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End point title

Part 2: Percent change from baseline in the absolute PGA scores at each visit

End point description

The PGA score is used to assess the overall severity of the psoriasis lesions at the time of evaluation. Overall lesions will be graded for erythema, induration, and scale based on 6-point scale ranging from 0 (clear) to 5 (severe). The sum of 3 scales will be divided by 3 to obtain final PGA score. Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline is calculated by subtracting post-dose value baseline value. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline; Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percent change
arithmetic mean (standard deviation)
Week 20/24 (n= 37, 100)	-55.86 ( 30.80 )	-41.77 ( 22.80 )
Week 32/36 (n= 30, 103)	-55.83 ( 32.69 )	-62.17 ( 26.07 )
Week 40 (n= 30, 100)	-50.28 ( 32.57 )	-70.93 ( 26.99 )

No statistical analyses for this end point

Secondary: Part 2: Percent change from baseline in the absolute ScPGA and PPPGA scores at each visit

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End point title

Part 2: Percent change from baseline in the absolute ScPGA and PPPGA scores at each visit

End point description

The scPGA score is used to assess average severity of scalp psoriasis lesions. scPGA is also 5- point scale ranging from 0 (clear) to 4 (severe), higher score indicate severe scalp psoriasis lesions. Only in participants with scalp involvement, the scPGA assessment was performed. PPPGA score is used to assess average severity of psoriasis lesions on hands and/or feet. PPPGA is a 5- point scale ranging from 0 (clear) to 4 (severe), higher score indicates severe psoriasis lesions on hands and/or feet. Only in participants with palmar or plantar involvement, PPPGA assessment was performed. Baseline value is defined as values collected at Week 1 of Part 1 of study. Percent Change from Baseline=Change from baseline/baseline value*100. If baseline value was 0, percent change from baseline was not computed. ITT population for Part 2 = all patients entering Part 2 of study who took at least one dose of assigned Part 2 study medication. Here, "n"= number of subjects analysed for each category.

End point type

Secondary

End point timeframe

Baseline; Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percent change
arithmetic mean (standard deviation)
PPPGA: Week 20/24 (n= 6, 25)	-77.78 ( 40.37 )	-61.00 ( 39.80 )
PPPGA: Week 32/36 (n= 5, 27)	-86.67 ( 29.81 )	-84.57 ( 29.12 )
PPPGA: Week 40 (n= 5, 27)	-80.00 ( 44.72 )	-84.88 ( 27.45 )
ScPGA: Week 20/24 (n= 32, 85)	-69.01 ( 40.34 )	-47.06 ( 32.22 )
ScPGA: Week 32/36 (n= 25, 87)	-70.67 ( 44.69 )	-71.55 ( 33.61 )
ScPGA: Week 40 (n= 27, 86)	-63.89 ( 43.30 )	-73.74 ( 30.48 )

No statistical analyses for this end point

Secondary: Part 2: Percentage of subjects achieving Dermatology Quality of Life Index (DLQI) scores of 0 or 1 at Week 32 and Week 40 Visits

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End point title

Part 2: Percentage of subjects achieving Dermatology Quality of Life Index (DLQI) scores of 0 or 1 at Week 32 and Week 40 Visits

End point description

DLQI is a questionnaire which is to evaluate the impact on participant's quality of life due to psoriasis. It is composed of ten items related to symptoms, feelings, daily activities, leisure, working or studying activities, personal relationships and opinions about dermatological treatment. Each item is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 32 and 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percentage of subjects
number (not applicable)
Week 32 (n=28,101)	50.0	45.5
Week 40 (n=29,100)	51.7	56.0

No statistical analyses for this end point

Secondary: Part 2: Absolute DLQI score at Week 32 and Week 40 Visits

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End point title

Part 2: Absolute DLQI score at Week 32 and Week 40 Visits

End point description

DLQI is a questionnaire which is to evaluate the impact on participant's quality of life due to psoriasis. It is composed of ten items related to symptoms, feelings, daily activities, leisure, working or studying activities, personal relationships and opinions about dermatological treatment. Each item is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 32, 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: units on a scale
arithmetic mean (standard deviation)
Week 32 (n= 28, 101)	3.50 ( 4.84 )	3.75 ( 4.94 )
Week 40 (n= 29, 100)	3.41 ( 5.21 )	3.36 ( 4.96 )

No statistical analyses for this end point

Secondary: Part 2: Percent change from baseline in the absolute DLQI score at Week 32 and Week 40 Visits

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End point title

Part 2: Percent change from baseline in the absolute DLQI score at Week 32 and Week 40 Visits

End point description

DLQI is a questionnaire which is to evaluate the impact on participant's quality of life due to psoriasis. It is composed of ten items related to symptoms, feelings, daily activities, leisure, working or studying activities, personal relationships and opinions about dermatological treatment. Each item is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30. Percent Change from Baseline=Change from baseline/baseline value*100. If baseline value was 0, percent change from baseline was not computed. The ITT population for Part 2 was defined as all patients entering Part 2 of study who took at least one dose of assigned Part 2 study medication. Here, "n"=number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline, Week 32 and 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percent change
arithmetic mean (standard deviation)
Week 32 (n= 28, 99)	-68.47 ( 30.69 )	-65.83 ( 46.56 )
Week 40 (n= 29, 98)	-65.82 ( 44.70 )	-66.78 ( 48.67 )

No statistical analyses for this end point

Secondary: Part 2: Absolute Skindex-16 score at Week 32 and Week 40 Visits

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End point title

Part 2: Absolute Skindex-16 score at Week 32 and Week 40 Visits

End point description

Skindex is the dermatological instruments to measure dermatology-specific Health-Related Quality of Life (HRQoL). The 16-item Skindex questionnaire is divided into three domains: questions related to the participant's symptoms (1-4), emotions (5-11), and functioning (12-16). Each question asks the participant to quantify how much a specific aspect of their skin condition bothered them in the week prior to administration of the Skindex-16. The questions are answered on a scale from 0 (never bothered) to 6 (always bothered) with a total possible score ranging from 0 (best HRQoL) to 96 (worst HRQoL). Each item is then transformed to a linear scale from 0 to 100. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 32 and 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: units on a scale
arithmetic mean (standard deviation)
Week 32 (n= 28, 101)	17.86 ( 24.30 )	20.24 ( 23.94 )
Week 40 (n= 29, 100)	19.40 ( 24.75 )	18.97 ( 24.11 )

No statistical analyses for this end point

Secondary: Part 2: Percent change from baseline in the absolute Skindex-16 score at Week 32 and Week 40 Visits

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End point title

Part 2: Percent change from baseline in the absolute Skindex-16 score at Week 32 and Week 40 Visits

End point description

Skindex is dermatological instruments to measure dermatology-specific Health-Related Quality of Life (HRQoL). The 16-item Skindex questionnaire is divided into three domains: questions related to participant's symptoms (1-4), emotions (5-11), and functioning (12-16). Each question asks the participant to quantify how much a specific aspect of their skin condition bothered them in week prior to administration of the Skindex-16. The questions are answered on a scale from 0 (never bothered) to 6 (always bothered) with a total possible score ranging from 0 (best HRQoL) to 96 (worst HRQoL). Each item is then transformed to linear scale from 0 to 100. Percent Change from Baseline=Change from baseline/baseline value*100. If baseline value was 0, percent change from baseline was not computed. The ITT population for Part 2 was defined as all patients entering Part 2 of study who took at least one dose of assigned Part 2 study medication. Here, "n"=number of subjects analysed for each category.

End point type

Secondary

End point timeframe

Baseline, Week 32 and Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percent change
arithmetic mean (standard deviation)
Week 32 (n= 27, 95)	-70.66 ( 33.90 )	-53.59 ( 131.66 )
Week 40 (n= 28, 94)	-67.48 ( 34.06 )	-54.01 ( 114.09 )

No statistical analyses for this end point

Secondary: Part 2: Absolute pruritus-VAS score at each visit

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End point title

Part 2: Absolute pruritus-VAS score at each visit

End point description

The pruritus-VAS is used to assess the pruritus by ticking the scale, which describes pruritus the best. The pruritus-VAS is a single-item continuous scale comprised of a 10 centimeter (cm) [(100 millimeter (mm)] horizontal/vertical line anchored by two verbal descriptors, one for each symptom extreme. For pruritus intensity, the scale is anchored by "no pruritus" (score of 0) and "worst imaginable pruritus" (score of 100 mm). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Change from baseline is calculated by subtracting post-dose value baseline value. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: units on a scale
arithmetic mean (standard deviation)
Week 20/24 (n= 35, 102)	1.77 ( 1.68 )	3.73 ( 2.74 )
Week 32/36 (n= 28, 101)	1.82 ( 2.13 )	2.46 ( 2.53 )
Week 40 (n= 29, 100)	1.97 ( 2.37 )	2.13 ( 2.44 )

No statistical analyses for this end point

Secondary: Part 2: Percent change from baseline in the absolute pruritus-VAS score at each visit

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End point title

Part 2: Percent change from baseline in the absolute pruritus-VAS score at each visit

End point description

The pruritus-VAS is used to assess the pruritus by ticking the scale, which describes pruritus the best. The pruritus-VAS is a single-item continuous scale comprised of a 10 centimeter (cm) [(100 millimeter (mm)] horizontal/vertical line anchored by two verbal descriptors, one for each symptom extreme. For pruritus intensity, the scale is anchored by "no pruritus" (score of 0) and "worst imaginable pruritus" (score of 100 mm). Baseline value is defined as values collected at Week 1 of Part 1 of the study. Percent Change from Baseline=Change from baseline/baseline value*100. If baseline value was 0, percent change from baseline was not computed. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline; Week 20/24; Week 32/36; Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percent change
arithmetic mean (standard deviation)
Week 20/24 (n= 33, 96)	-62.69 ( 34.953 )	-14.25 ( 112.46 )
Week 32/36 (n= 27, 95)	-60.33 ( 44.02 )	-37.56 ( 110.72 )
Week 40 (n= 28, 94)	-54.02 ( 58.39 )	-44.50 ( 117.03 )

No statistical analyses for this end point

Secondary: Part 2: Absolute MOSS score at Week 40 Visit

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End point title

Part 2: Absolute MOSS score at Week 40 Visit

End point description

The MOSS questionnaire consists of 12 items leading to 6 subscales or domains: sleep disturbance, sleep adequacy, daytime sleepiness, 'supposed or known' snoring, being awakened by shortness of breath or by a headache, and quantity of sleep. Subscales are standardized to yield scores from 0 to 100, with the exception of sleep quantity. Higher scores on the MOSS reflects more of the attribute indicated by the subscale name.The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication.

End point type

Secondary

End point timeframe

Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	29	100
Units: units on a scale
arithmetic mean (standard deviation)
Disturbance	29.53 ( 22.47 )	34.56 ( 21.38 )
Quantity	6.97 ( 1.02 )	6.87 ( 1.23 )
Adequacy	60.34 ( 24.34 )	57.75 ( 23.82 )
Shortness of breath/headache	13.79 ( 17.15 )	19.00 ( 22.51 )
Snoring	36.21 ( 33.80 )	42.75 ( 31.04 )
Somnolence	28.45 ( 20.72 )	31.67 ( 20.03 )

No statistical analyses for this end point

Secondary: Part 2: Percent change from baseline in the absolute MOSS score at Week 40 Visit

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End point title

Part 2: Percent change from baseline in the absolute MOSS score at Week 40 Visit

End point description

The MOSS questionnaire consists of 12 items leading to 6 subscales or domains: sleep disturbance, sleep adequacy, daytime sleepiness, 'supposed or known' snoring, being awakened by shortness of breath or by a headache, and quantity of sleep. Subscales are standardized to yield scores from 0 to 100, with the exception of sleep quantity. Higher scores on the MOSS reflects more of the attribute indicated by the subscale name. Percent Change from Baseline=Change from baseline/baseline value*100. If baseline value was 0, percent change from baseline was not computed. The ITT population for Part 2 was defined as all patients entering Part 2 of the study who took at least one dose of the assigned Part 2 study medication. Here, "n" signifies number of subjects analyzed for each category.

End point type

Secondary

End point timeframe

Baseline and Week 40

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: percent change
arithmetic mean (standard deviation)
Disturbance (n=28,100)	-16.61 ( 50.12 )	2.45 ( 85.52 )
Quantity (n=29,100)	3.61 ( 13.41 )	4.85 ( 21.12 )
Adequacy (n=28,99)	20.41 ( 73.70 )	20.86 ( 82.03 )
Shortness of breath/headache (n=11,54)	-18.18 ( 81.46 )	-29.32 ( 60.65 )
Snoring (n=20,80)	8.75 ( 72.22 )	-7.08 ( 56.41 )
Somnolence (n=28,97)	2.71 ( 73.96 )	21.89 ( 136.39 )

No statistical analyses for this end point

Secondary: Part 2: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

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End point title

Part 2: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs)

End point description

An Adverse event (AE) is defined as "any untoward medical occurrence in a clinical trial participant (regardless of the administration of the study drug and its causal relationship to it). An AE can therefore be any unfavourable and unintended medical occurrence during the participant's participation in the trial, including deterioration of a pre-existing medical condition, an abnormal clinically significant finding in a laboratory assessment, or an abnormal clinically significant finding in the physical examination or vital sign. Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward will be counted as TEAE. The Safety Analyses Set (SAF) was defined as all subjects who were included and took at least one dose of the study medication.

End point type

Secondary

End point timeframe

Up to Week 49

End point values	DMF treatment	Tildrakizumab treatment
Number of subjects analysed	37	103
Units: subjects	24	41

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to Week 49

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Part 1: Standard DMF treatment scheme

Reporting group description

Participants received DMF standard scheme from baseline to Week 16.

Reporting group title

Part 1: Simplified DMF treatment scheme

Reporting group description

Reporting group title

Part 2: DMF treatment

Reporting group description

Reporting group title

Part 2: Tildrakizumab treatment

Reporting group description

Serious adverse events	Part 1: Standard DMF treatment scheme	Part 1: Simplified DMF treatment scheme	Part 2: DMF treatment	Part 2: Tildrakizumab treatment
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 143 (3.50%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 103 (0.97%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 143 (0.00%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Chest pain
subjects affected / exposed	1 / 143 (0.70%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastric ulcer
subjects affected / exposed	1 / 143 (0.70%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	1 / 143 (0.70%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	1 / 143 (0.70%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Part 1: Standard DMF treatment scheme	Part 1: Simplified DMF treatment scheme	Part 2: DMF treatment	Part 2: Tildrakizumab treatment
Total subjects affected by non serious adverse events
subjects affected / exposed	123 / 143 (86.01%)	40 / 46 (86.96%)	24 / 37 (64.86%)	41 / 103 (39.81%)
Vascular disorders
Hot flush
subjects affected / exposed	10 / 143 (6.99%)	2 / 46 (4.35%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	10	3	0	0
Hypertension
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	1 / 37 (2.70%)	2 / 103 (1.94%)
occurrences all number	0	1	1	2
Flushing
subjects affected / exposed	40 / 143 (27.97%)	12 / 46 (26.09%)	2 / 37 (5.41%)	0 / 103 (0.00%)
occurrences all number	47	15	2	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	3 / 143 (2.10%)	2 / 46 (4.35%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	3	2	0	0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Psychiatric disorders
Sleep disorder
subjects affected / exposed	1 / 143 (0.70%)	0 / 46 (0.00%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	1	0	1	0
Investigations
Transaminases increased
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	1	0	1
Lymphocyte count decreased
subjects affected / exposed	7 / 143 (4.90%)	3 / 46 (6.52%)	1 / 37 (2.70%)	1 / 103 (0.97%)
occurrences all number	7	3	1	1
Weight increased
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
CD8 lymphocytes decreased
subjects affected / exposed	2 / 143 (1.40%)	0 / 46 (0.00%)	1 / 37 (2.70%)	2 / 103 (1.94%)
occurrences all number	2	0	1	2
CD4 lymphocytes decreased
subjects affected / exposed	0 / 143 (0.00%)	0 / 46 (0.00%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	0	0	1	0
Blood creatine phosphokinase increased
subjects affected / exposed	4 / 143 (2.80%)	0 / 46 (0.00%)	1 / 37 (2.70%)	1 / 103 (0.97%)
occurrences all number	4	0	1	1
Injury, poisoning and procedural complications
Vaccination complication
subjects affected / exposed	0 / 143 (0.00%)	2 / 46 (4.35%)	0 / 37 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	2	0	2
Traumatic arthropathy
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Meniscus injury
subjects affected / exposed	1 / 143 (0.70%)	0 / 46 (0.00%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	1	0	1	0
Nervous system disorders
Migraine
subjects affected / exposed	2 / 143 (1.40%)	2 / 46 (4.35%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	2	2	0	1
Paraesthesia
subjects affected / exposed	4 / 143 (2.80%)	2 / 46 (4.35%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	5	2	1	0
Headache
subjects affected / exposed	14 / 143 (9.79%)	6 / 46 (13.04%)	1 / 37 (2.70%)	6 / 103 (5.83%)
occurrences all number	15	7	2	6
Dizziness
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	1 / 143 (0.70%)	0 / 46 (0.00%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	1	0	1	0
Eosinophilia
subjects affected / exposed	1 / 143 (0.70%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	1	1	0	0
Lymphopenia
subjects affected / exposed	17 / 143 (11.89%)	3 / 46 (6.52%)	8 / 37 (21.62%)	3 / 103 (2.91%)
occurrences all number	17	3	8	3
Gastrointestinal disorders
Dry mouth
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Colitis
subjects affected / exposed	0 / 143 (0.00%)	0 / 46 (0.00%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	0	0	1	0
Diarrhoea
subjects affected / exposed	61 / 143 (42.66%)	12 / 46 (26.09%)	2 / 37 (5.41%)	1 / 103 (0.97%)
occurrences all number	64	14	2	1
Constipation
subjects affected / exposed	4 / 143 (2.80%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	4	1	0	0
Abdominal pain upper
subjects affected / exposed	34 / 143 (23.78%)	15 / 46 (32.61%)	0 / 37 (0.00%)	2 / 103 (1.94%)
occurrences all number	36	15	0	2
Abdominal pain
subjects affected / exposed	25 / 143 (17.48%)	7 / 46 (15.22%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	27	10	1	0
Toothache
subjects affected / exposed	2 / 143 (1.40%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	2	1	0	1
GI pain
subjects affected / exposed	4 / 143 (2.80%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	6	0	0	0
Vomiting
subjects affected / exposed	5 / 143 (3.50%)	2 / 46 (4.35%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	5	2	0	1
Nausea
subjects affected / exposed	14 / 143 (9.79%)	4 / 46 (8.70%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	15	4	1	0
Abdominal discomfort
subjects affected / exposed	5 / 143 (3.50%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	7	1	0	0
Gastritis
subjects affected / exposed	4 / 143 (2.80%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	5	1	0	0
GI disorder
subjects affected / exposed	15 / 143 (10.49%)	6 / 46 (13.04%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	16	6	0	0
Skin and subcutaneous tissue disorders
Skin swelling
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Seborrhoeic dermatitis
subjects affected / exposed	1 / 143 (0.70%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	1	1	0	1
Rash
subjects affected / exposed	3 / 143 (2.10%)	0 / 46 (0.00%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	3	0	0	0
Psoriasis
subjects affected / exposed	7 / 143 (4.90%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	8	1	0	1
Pruritus
subjects affected / exposed	9 / 143 (6.29%)	3 / 46 (6.52%)	0 / 37 (0.00%)	2 / 103 (1.94%)
occurrences all number	11	3	0	2
Renal and urinary disorders
Ketonuria
subjects affected / exposed	1 / 143 (0.70%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	1	1	0	1
Glycosuria
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	1 / 143 (0.70%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	2	1	0	1
Musculoskeletal pain
subjects affected / exposed	3 / 143 (2.10%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	4	0	0	1
Back pain
subjects affected / exposed	1 / 143 (0.70%)	0 / 46 (0.00%)	1 / 37 (2.70%)	2 / 103 (1.94%)
occurrences all number	1	0	1	2
Muscle tightness
subjects affected / exposed	1 / 143 (0.70%)	0 / 46 (0.00%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	1	0	1	0
Arthralgia
subjects affected / exposed	5 / 143 (3.50%)	0 / 46 (0.00%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	5	0	0	1
Infections and infestations
Herpes zoster
subjects affected / exposed	1 / 143 (0.70%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	1	1	0	1
Gastroenteritis
subjects affected / exposed	2 / 143 (1.40%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	2	1	0	1
Diverticulitis
subjects affected / exposed	0 / 143 (0.00%)	0 / 46 (0.00%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	0	0	1	0
Cystitis
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	0	1	1	0
Hordeolum
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Coronavirus infection
subjects affected / exposed	4 / 143 (2.80%)	1 / 46 (2.17%)	0 / 37 (0.00%)	5 / 103 (4.85%)
occurrences all number	4	1	0	5
Tonsillitis
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	1	0	1
Tinea versicolour
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Subcutaneous abscess
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0
Sinusitis bacterial
subjects affected / exposed	0 / 143 (0.00%)	0 / 46 (0.00%)	1 / 37 (2.70%)	0 / 103 (0.00%)
occurrences all number	0	0	1	0
Nasopharyngitis
subjects affected / exposed	11 / 143 (7.69%)	3 / 46 (6.52%)	4 / 37 (10.81%)	2 / 103 (1.94%)
occurrences all number	11	3	4	2
Metabolism and nutrition disorders
Hyperuricaemia
subjects affected / exposed	1 / 143 (0.70%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	1	1	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 143 (0.00%)	1 / 46 (2.17%)	0 / 37 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

20 Sep 2019

Amendment 1: -Included laboratory parameters for haematology: differential count (absolute and relative) for CD4+ and CD8+ T lymphocytes as well as CD4/CD8 ratio. -Changed the withdrawal criterion about the violation of eligibility criteria to make this criterion the same for all centres. -Clarified the exclusion criterion about the excipient (criterion number 5). -Included the rational for simplified DMF scheme and the non-washout period between the DMF and tildrakizumab administration. -Clarified the wording of exclusion criteria number 13 and 14. -Eliminated albumin as a urinalysis parameter in the laboratory safety measurements. -Clarified information about the subsequent medication information to be collected after the last dose of the study drug. -Aligned the contraceptive methods advice in the protocol with those in tildrakizumab and DMF SmPCs. -To clarify the destruction of the remaining study medication; license from company in charge of the destruction was requested.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
31 Mar 2020	The screening and recruitment of new participants was paused due to the ongoing SARS-CoV-2 pandemic in Europe. The decision was based on commitment to protect the safety and health of study participants, site staff and their families and the challenges expressed by the investigators in regards to enrolling participants during the pandemic.	13 May 2020

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: An open-label, randomized, Phase IV study, to assess the efficacy and safety of tildrakizumab in patients with moderate to severe chronic plaque psoriasis who are non-responders to dimethyl fumarate therapy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 2: Percentage of subjects who were non-responders to DMF at Week 16 that were treated with tildrakizumab and achieved a PASI 75 at Week 40

Primary: Part 2: Percentage of subjects who were non-responders to DMF at Week 16 that were treated with tildrakizumab and achieved a PASI 75 at Week 40

Secondary: Part 1: Percentage of subjects achieving PASI 50, PASI 75 and PASI 90 responses at Week 8 and Week 16 Visits

Secondary: Part 1: Percentage of subjects achieving PASI 50, PASI 75 and PASI 90 responses at Week 8 and Week 16 Visits

Secondary: Part 1: Percentage of subjects achieving absolute PASI scores of ≤5, ≤3 and ≤1 at Week 8 and Week 16 Visits

Secondary: Part 1: Percentage of subjects achieving absolute PASI scores of ≤5, ≤3 and ≤1 at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute PASI score at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute PASI score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute PASI score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute PASI score at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute Body Surface Area (BSA) Score at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute Body Surface Area (BSA) Score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from Baseline in Absolute Body Surface Area (BSA) Score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from Baseline in Absolute Body Surface Area (BSA) Score at Week 8 and Week 16 Visits

Secondary: Part 1: Percentage of subjects achieving PGA scores of 0 or 1 at Week 8 and Week 16 Visits

Secondary: Part 1: Percentage of subjects achieving PGA scores of 0 or 1 at Week 8 and Week 16 Visits

Secondary: Part 1: Percentage of subjects achieving Scalp Physician Global Assessment (scPGA) and Palmoplantar Physician's Global Assessment (PPPGA) Scores of 0 or 1 at Week 8 and Week 16 Visits

Secondary: Part 1: Percentage of subjects achieving Scalp Physician Global Assessment (scPGA) and Palmoplantar Physician's Global Assessment (PPPGA) Scores of 0 or 1 at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute PGA scores at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute PGA scores at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute ScPGA and PPPGA scores at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute ScPGA and PPPGA scores at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute PGA scores at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute PGA scores at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute ScPGA and PPPGA scores at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute ScPGA and PPPGA scores at Week 8 and Week 16 Visits

Secondary: Part 1: Percentage of subjects achieving Dermatology Quality of Life Index (DLQI) scores of 0 or 1 at Week 8 and Week 16 Visits

Secondary: Part 1: Percentage of subjects achieving Dermatology Quality of Life Index (DLQI) scores of 0 or 1 at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute DLQI score at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute DLQI score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute DLQI score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute DLQI score at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute Skindex-16 score at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute Skindex-16 score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute Skindex-16 score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute Skindex-16 score at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute pruritus-VAS score at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute pruritus-VAS score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute pruritus-VAS score at Week 8 and Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute pruritus-VAS score at Week 8 and Week 16 Visits

Secondary: Part 1: Absolute Medical Outcomes Study Score (MOSS) at Week 16 Visit

Secondary: Part 1: Absolute Medical Outcomes Study Score (MOSS) at Week 16 Visit

Secondary: Part 1: Change from baseline in the absolute MOSS score at Week 16 Visits

Secondary: Part 1: Change from baseline in the absolute MOSS score at Week 16 Visits

Secondary: Part 2: Percentage of subjects achieving PASI 50, PASI 75 and PASI 90 responses

Secondary: Part 2: Percentage of subjects achieving PASI 50, PASI 75 and PASI 90 responses

Secondary: Part 2: Percentage of subjects achieving absolute PASI scores of ≤5, ≤3 and ≤1

Secondary: Part 2: Percentage of subjects achieving absolute PASI scores of ≤5, ≤3 and ≤1

Secondary: Part 2: Absolute PASI score at each visit

Secondary: Part 2: Absolute PASI score at each visit

Secondary: Part 2: Change from baseline in the absolute PASI score at each visit

Secondary: Part 2: Change from baseline in the absolute PASI score at each visit

Secondary: Part 2: Percent change from baseline in the absolute PASI score at each visit

Secondary: Part 2: Percent change from baseline in the absolute PASI score at each visit

Secondary: Part 2: Absolute Body Surface Area (BSA) Score at each visit

Secondary: Part 2: Absolute Body Surface Area (BSA) Score at each visit

Secondary: Part 2: Change from baseline in the absolute BSA score at each visit

Secondary: Part 2: Change from baseline in the absolute BSA score at each visit

Secondary: Part 2: Percentage of subjects achieving PGA scores of 0 or 1 at each visit

Secondary: Part 2: Percentage of subjects achieving PGA scores of 0 or 1 at each visit

Secondary: Part 2: Percentage of subjects achieving ScPGA and PPPGA scores of 0 or 1 at each visit

Secondary: Part 2: Percentage of subjects achieving ScPGA and PPPGA scores of 0 or 1 at each visit

Secondary: Part 2: Absolute PGA scores at each visit

Secondary: Part 2: Absolute PGA scores at each visit

Secondary: Part 2: Percent change from baseline in the absolute PGA scores at each visit

Secondary: Part 2: Percent change from baseline in the absolute PGA scores at each visit

Secondary: Part 2: Percent change from baseline in the absolute ScPGA and PPPGA scores at each visit

Secondary: Part 2: Percent change from baseline in the absolute ScPGA and PPPGA scores at each visit

Secondary: Part 2: Percentage of subjects achieving Dermatology Quality of Life Index (DLQI) scores of 0 or 1 at Week 32 and Week 40 Visits

Secondary: Part 2: Percentage of subjects achieving Dermatology Quality of Life Index (DLQI) scores of 0 or 1 at Week 32 and Week 40 Visits

Clinical Trial Results:
An open-label, randomized, Phase IV study, to assess the efficacy and safety of tildrakizumab in patients with moderate to severe chronic plaque psoriasis who are non-responders to dimethyl fumarate therapy